'Boot camp' enzyme prevents autoimmune conditions

'Boot camp' enzyme prevents autoimmune conditions

Illuminate newsletter header, Winter 2022
June 2022
WEHI researchers have identified an enzyme in the thymus that is essential for immune T cells to correctly identify threats, safeguarding them from going rogue and attacking healthy tissue in the body.

Photo of Daniel Gray and Tim Thomas at WEHI
Associate Professor Daniel Gray (left) and
Associate Professor Tim Thomas led research that revealed
how the enzyme KAT7 helps train immune T cells.

The thymus is an important organ where immune T cells learn to fight infection. The new findings revealed that the enzyme KAT7 is necessary to activate thousands of genes required for ‘training’ T cells not to attack healthy tissue.

Without proper training, T cells are at risk of sabotaging the immune system, which could lead to autoimmune conditions such as type 1 diabetes or multiple sclerosis.

A ‘preview’ of threats

The thymus is like a ‘boot camp’ where T cells are trained to identify and fight pathogens, and taught not to attack healthy organs. T cells are shown a ‘preview’ of all the various components of healthy tissues they could encounter once they leave the thymus.

While it was previously known that the Autoimmune Regulator (AIRE) protein activated the thousands of genes needed for this preview, it was unclear how this protein knew which genes to ‘switch on’ – until now.

The new research was led by former WEHI PhD student Dr Melanie Heinlein, with Associate Professor Tim Thomas and Associate Professor Daniel Gray from WEHI in collaboration with researchers at Monash University and the Weizmann Institute of Science in Israel.

“Like a training coordinator, the KAT7 enzyme directs AIRE to the genes that must be activated for the ‘boot camp’ to run smoothly. The enzyme does this by tagging the genes that AIRE needs to ‘switch on’ for the preview of the body’s proteins to work,” Dr Heinlein said.

Importance of KAT7

Associate Professor Tim Thomas said the enzyme’s crucial role in keeping T cells to task was made clear when the researchers used a new drug to block its function.

“We showed how a KAT7 inhibitor was able to stop AIRE from switching on the genes needed to properly train T cells,” he said.

“Stopping this process sent the immune system into overdrive, leading to T cells going rogue and causing a range of autoimmune conditions in pre-clinical models.”

Treatment potential

Associate Professor Daniel Gray said the discovery could lead to new treatments that target KAT7 to modify the training of T cells, so they can either be stopped from causing autoimmunity or boosted to fight disease.

“Potential applications of this knowledge include autoimmune diseases such as type 1 diabetes and multiple sclerosis, as well as cancer immunotherapy,” he said.

“In the latter scenario, the immune system could be supercharged to combat cancer by blocking KAT7 in the thymus.”

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